Background and Importance Fluoropyrimidines in solid tumours are metabolised by dihydropyrimidine dehydrogenase (DPD) enzyme, encoded by DPYD gene. Up to 3-6% of the population have a DPYD variant, which, without appropriate dose reduction, will lead to severe toxicity/death[i].
Since 2020 the regulatory agencies in Europe and the UK recommend all patients to be tested for DPD deficiency before initiation to minimise the risk of these reactions[ii],[iii].
Five London cancer providing trusts (CPT) assured testing was being performed[iv].
The North Thames Genomic Medicines Service Alliance (NTGMSA) is one of the seven in the UK working on a national project to ensure equitable implementation of DPYD pharmacogenomic testing.
Aim and Objectives To establish that all CPT within NTGMSA are safely implementing DPYD testing.
Material and Methods Five questions analysed from national survey:
Who is involved in checking the result of the DPYD genetic test?;
Who makes dose adjustments?;
Is chemotherapy prescribed prior the test report?;
Is chemotherapy delayed when results are pending?
Results Within NTGMSA all 14 CPT responded. Everyone provides DPYD testing for all cancer indications which include fluoropyrimidine treatment. Multiple healthcare professionals check and action the test results, following dose reductions, following guidance. Chemotherapy is prescribed prior receiving the genetic report in 10 CPT. 6 hospitals would delay administration when result is missing.
Conclusion and Relevance There is a rich multidisciplinary involvement in checking the results of the test, including making the correct dose adjustments. The use of DPYD tests to prevent chemotherapy toxicity follows a safe and robust pathway within our region.
References and/or Acknowledgements [i] UK Chemotherapy Board, ‘Personalised Medicine Approach For Fluoropyrimidine-based Therapies,’ 2020. [Online]. Available: https://www.theacp.org.uk/userfiles/file/resources/dpd-testing-ukcb-july-2020-updated.pdf
[ii] EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine | European Medicines Agency (europa.eu)
[iii] 5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity – GOV.UK (www.gov.uk)
[iv] Nijjar R, Shaunak N, Mahmoud S, Thwaites B, Desai M, Ajediti C, Brown A, Yeoh I, Patel T, Masento S. 'A collaborative audit on DPYD testing of all patients initiated on fluoropyrimidines (5-fluorouracil, capecitabine and oral prodrug tegafur) across 5 London teaching hospitals' Abstract; Journal of Oncology Pharmacy Practice, 2021 Suppl & Oral Poster Presentation
Conflict of Interest No conflict of interest